CD4 T cells kill melanoma cells by mechanisms that are independent of Fas (CD95).
Previous studies have shown that CD4 T cells are associated with regression in primary melanoma and rejection of tumors in adoptive transfer models. The mechanism by which they mediate their anti-tumor effects remains unclear, and some studies have suggested that Fas ligand (FasL)/Fas interactions were involved. In the present study, we have examined the cytotoxic mechanism involved in CD4 T-cell killing of melanoma cells and, in particular, the role of FasL/Fas interactions in this killing. We show that the CD4 T cells in 4 clones of T cells induced apoptosis in autologous melanoma cells by MHC-restricted mechanisms but lysed an allogeneic melanoma cell by a non-apoptotic mechanism. Melanoma cells expressed both Fas and FasL, but killing of melanoma cells did not involve Fas/FasL interactions. This was shown by a lack of correlation between Fas expression and susceptibility to lysis and by failure of a monoclonal antibody to Fas to block killing by the CD4 T cells, though the latter expressed FasL. Recombinant FasL did not induce killing of melanoma cells.
Thomas
W D
WD
Department of Surgery, John Hunter Hospital, Newcastle, Australia.
Hersey
P
P
D017209:Apoptosis / Q000276:immunology*; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002118:Calcium / Q000378:metabolism; D002453:Cell Cycle; D003602:Cytotoxicity, Immunologic; D006801:Humans; D016219:Immunotherapy, Adoptive; D008285:Major Histocompatibility Complex / Q000276:immunology; D008297:Male; D008545:Melanoma / Q000378:metabolism / Q000473:pathology* / Q000628:therapy*; D008875:Middle Aged; D008969:Molecular Sequence Data; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000502:physiology*
D019014:fas Receptor; D002118:Calcium